Abstract:
:Treatment of malignant gliomas represents one of the most formidable challenges in oncology. The combination of surgery, radiation, and chemotherapy yields median survivals of less than one year. Here we demonstrate the use of a minimally invasive surgical technique, convection-enhanced delivery (CED), for local administration of a novel nanoparticle liposome containing topotecan. CED of this liposomal topotecan (Ls-TPT) resulted in extended brain tissue retention (t1/2 = 1.5 days), whereas free topotecan was rapidly cleared (t1/2 = 0.1 days) after CED. The favorable pharmacokinetic profile of extended topotecan release for about seven days, along with biodistribution featuring perivascular accumulation of the nanoparticles, provided, in addition to the known topoisomerase I inhibition, an effective antiangiogenic therapy. In the rat intracranial U87MG tumor model, vascular targeting of Ls-TPT with CED was associated with reductions in laminin expression and vascular density compared to free topotecan or control treatments. A single CED treatment on day 7 showed that free topotecan conferred no survival benefit versus control. However, Ls-TPT produced a significant (P = 0.0002) survival benefit, with six of seven complete cures. Larger U87MG tumors, where CED of Ls-TPT on day 12 resulted in one of six cures, indicated the necessity to cover the entire tumor with the infused therapeutic agent. CED of Ls-TPT was also efficacious in the intracranial U251MG tumor model (P = 0.0005 versus control). We conclude that the combination of a novel nanoparticle Ls-TPT and CED administration was very effective in treating experimental brain tumors.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Saito R,Krauze MT,Noble CO,Drummond DC,Kirpotin DB,Berger MS,Park JW,Bankiewicz KSdoi
10.1215/15228517-2006-001subject
Has Abstractpub_date
2006-07-01 00:00:00pages
205-14issue
3eissn
1522-8517issn
1523-5866pii
15228517-2006-001journal_volume
8pub_type
杂志文章相关文献
NEURO-ONCOLOGY文献大全abstract:BACKGROUND:Micro (mi)RNAs are key regulators of gene expression and offer themselves as biomarkers for cancer development and progression. Meningioma is one of the most frequent primary intracranial tumors. As of yet, there are limited data on the role of miRNAs in meningioma of different histological subtypes and the ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov014
更新日期:2015-09-01 00:00:00
abstract::Protein kinase C alpha (PKC-alpha) is a cytoplasmic serine threonine kinase involved in regulating cell differentiation and proliferation. Aprinocarsen is an antisense oligonucleotide against PKC-alpha that reduces PKC-alphain human cell lines and inhibits a human glioblastoma tumor cell line in athymic mice. In this ...
journal_title:Neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1215/S1152851703000353
更新日期:2005-01-01 00:00:00
abstract:Background:Glioblastoma (GBM) is one of the most common, aggressive, and invasive human brain tumors. There are few reliable mechanism-based therapeutic approaches for GBM patients. The transcriptional repressor RE1 silencing transcriptional factor (REST) regulates the oncogenic properties of a class of GBM stem-like c...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now232
更新日期:2017-04-01 00:00:00
abstract::The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survi...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/now127
更新日期:2016-08-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) gene amplification and activating mutations are common findings in glioblastomas. EGFR is at the top of a downstream signaling cascade that regulates important characteristics of glioblastoma cells, including cellular proliferation, migration, and survival. Targeting EGFR has th...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nou222
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:EORTC study 22033-26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or Temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of radiotherapy on memory functioning, this stu...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noaa252
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:Meningiomas are the most commonly diagnosed primary intracranial neoplasms. Despite significant advances in modern therapies, the management of malignant meningioma and skull base meningioma remains a challenge. Thus, the development of new treatment modalities is urgently needed for these difficult-to-treat...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not007
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Isocitrate dehydrogenase (IDH) mutation status has emerged as an important prognostic marker in gliomas. Currently, reliable IDH mutation determination requires invasive surgical procedures. The purpose of this study was to develop a highly accurate, MRI-based, voxelwise deep-learning IDH classification netw...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noz199
更新日期:2020-03-05 00:00:00
abstract::PDGFRA is a critical gene in glioma biology. Similar to EGFR, PDGFRA has been shown to be overexpressed, amplified, mutated, or truncated in gliomas, particularly glioblastomas. In addition, PDGFRA has been recently shown to be rearranged in glioblastoma. However, the frequency, cooccurrence, and clinical value of PDG...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos217
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND:We sought to determine the surgical treatment and functional outcome and identify the predictors of survival in a retrospective cohort of patients with spinal cord ependymoma using data collected from the Korea Spinal Oncology Research Group database. METHODS:The data regarding 88 patients who had been surg...
journal_title:Neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1093/neuonc/not038
更新日期:2013-07-01 00:00:00
abstract::The objective of this study was to evaluate whether longitudinal levels of serum YKL-40 correlate with disease status or survival in adults with gliomas. Patients with histologically confirmed gliomas were eligible for this longitudinal study. Serum samples were collected prospectively and concurrently with MRI scans ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor117
更新日期:2011-11-01 00:00:00
abstract::The exact incidence of pineal germ-cell tumors is largely unknown. The tumors are rare, and the number of patients with these tumors, as reported in clinical series, has been limited. The goal of this study was to describe pineal germ-cell tumors in a large number of patients, using data from available brain tumor dat...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2007-054
更新日期:2008-04-01 00:00:00
abstract::Vestibular schwannomas (VS) arising sporadically or in patients with neurofibromatosis type 2 (NF2) consistently lack expression of Merlin, a tumor suppressor. Conventional treatment options include surgery and radiotherapy but there is no validated medical option. Recent evidence suggests that Merlin deficiency may r...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noq012
更新日期:2010-08-01 00:00:00
abstract::The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving a...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/2.2.114
更新日期:2000-04-01 00:00:00
abstract::Angiogenesis is necessary for tumor growth beyond a volume of approximately 2 mm(3). This observation, along with the accessibility of tumor vessels to therapeutic targeting, has resulted in a research focus on inhibitors of angiogenesis. A number of endogenous inhibitors of angiogenesis are found in the body. Some of...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1215/S115285170400119X
更新日期:2005-04-01 00:00:00
abstract::Grade II gliomas are morphologically and clinically heterogeneous tumors for which histopathological typing remains the major tool for clinical classification. To what extent the major histological subtypes - astrocytomas, oligodendrogliomas, and oligoastrocytomas - constitute true biological entities is largely unres...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2007-041
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:To examine the efficacy of valproic acid (VPA) given either with or without levetiracetam (LEV) on seizure control and on survival in patients with glioblastoma multiforme (GBM) treated with chemoradiation. METHODS:A retrospective analysis was performed on 291 patients with GBM. The efficacies of VPA and LE...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not057
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:While standards for the treatment of newly diagnosed glioblastomas exist, therapeutic regimens for tumor recurrence remain mostly individualized. The role of a surgical resection of recurrent glioblastomas remains largely unclear at present. This study aimed to assess the effect of repeated resection of recu...
journal_title:Neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1093/neuonc/nov145
更新日期:2016-01-01 00:00:00
abstract::A 67-year-old man presented with a 7-month history of insidiously progressive chorea, ataxia, and vertigo. Neurologic examination revealed deficits referable to the basal nuclei, cerebellar vermis, and vestibular nuclei. Small-cell lung cancer was diagnosed by fine-needle biopsy of a parahilar mass. After chemotherapy...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/4.3.192
更新日期:2002-07-01 00:00:00
abstract:BACKGROUND:Expression of programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) across glioma grades is undocumented, and their interactions with commonly expressed genetic and epigenetic alterations are undefined but nonetheless highly relevant to combinatorial treatments. METHODS:Patients with CNS ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now132
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:Cognitive dysfunction is common among patients with brain tumors and can be associated with the disease and treatment with radiotherapy and chemotherapy. However, little is known about genetic risk factors that may moderate the vulnerability for developing cognitive dysfunction. In this study, we examined th...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now057
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:Glioblastoma multiforme with an oligodendroglial component (GBMO) has been recognized in the World Health Organization classification-however, the diagnostic criteria, molecular biology, and clinical outcome of primary GBMO remain unclear. Our aim was to investigate whether primary GBMO is a distinct clinico...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not125
更新日期:2013-12-01 00:00:00
abstract:Background:Advances from glioma stemlike cell (GSC) research, though increasing our knowledge of glioblastoma (GBM) biology, do not influence clinical decisions yet. We explored the translational power of GSC-enriched cultures from patient-derived tumorspheres (TS) in predicting treatment response. Methods:The relatio...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now304
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision makin...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou083
更新日期:2014-11-01 00:00:00
abstract:BACKGROUND:Cisplatin-Induced Peripheral Neuropathy (CIPN) is a frequent serious dose-dependent adverse event that can determine dosage limitations for cancer treatment. CIPN severity correlates with the amount of platinum detected in sensory neurons of the dorsal root ganglia (DRG). However, the exact pathophysiology o...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noaa151
更新日期:2020-06-29 00:00:00
abstract::This paper explicates the impact of tumor capillary permeability for glioma World Health Organization (WHO) grades II to IV on brain-penetrant drug entry and distribution within the tumor and the brain adjacent to tumor (leading edge). In addition, we consider the distribution of non-brain penetrant drugs and how, in ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noy018
更新日期:2018-04-09 00:00:00
abstract:BACKGROUND:Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is cont...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not218
更新日期:2014-04-01 00:00:00
abstract::A growing body of epidemiologic and tumor genomic research has identified an important role for telomere maintenance in glioma susceptibility, initiation, and prognosis. Telomere length has long been investigated in relation to cancer, but whether longer or shorter telomere length might be associated with glioma risk ...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nov082
更新日期:2015-11-01 00:00:00
abstract:BACKGROUND:Higher-grade meningiomas (HGMs; World Health Organization grades II and III) pose a clinical problem due to high recurrence rates and the absence of effective therapy. Preclinical development of novel therapeutics requires a disease model that recapitulates the genotype and phenotype of patient HGM. Oncolyti...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now031
更新日期:2016-09-01 00:00:00
abstract::People with neurofibromatosis 1 (NF1) have multiple benign neurofibromas and a 10% lifetime risk of developing malignant peripheral nerve sheath tumors (MPNSTs). Most MPNSTs develop from benign plexiform neurofibromas, so the burden of benign tumors may be a risk factor for developing MPNST. We studied 13 NF1 patients...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2008-011
更新日期:2008-08-01 00:00:00